Pharmacokinetic profile of children with haemophilia A receiving low-dose FVIII prophylaxis in Indonesia: A single centre experience.

Abstract

Pharmacokinetic (PK) studies of low-dose prophylaxis (LDP) of coagulation factor VIII (FVIII) in children with severe haemophilia A (SHA) are scarce. This study aims to investigate the PK profile of children with SHA receiving LDP of FVIII. Paediatric patients receiving FVIII infusions (10IU/kg twice weekly) were included. PK profiles were estimated using the Web Accessible Population Pharmacokinetic Service for Haemophilia (WAPPS-Haemo). The primary outcomes were the terminal half-life (t1/2 ), concentration-time profile, and time to reach an FVIII level of<1%. The secondary outcome was the suggested dosing interval of FVIII prophylaxis based on the individual PK profile. Twenty-five patients were recruited; their mean age was 12.3±3.0 years. The t1/2 differed among patients receiving LDP of FVIII twice weekly, with a median of t1/2 was 14.8 h (IQR 12.6-16). The median time to reach an FVIII level of<1% was 73.8 h (IQR 58.8-80.3). Most patients could maintain a trough level of FVIII>1% longer than 48h. At 72-96h, patients needed a second dose of FVIII infusion because the FVIII level was<1%. The suggested dosing interval of FVIII prophylaxis ranged from daily to every 96h, depending on the individual PK profile. Our study identified inter-individual differences in the PK parameters using LDP of FVIII twice weekly. The inter-individual results in different dosing intervals advise the timing of LDP. Estimating individual PK parameters enables the identification of the optimal prophylaxis frequency to prevent bleedings.